ccmE

Summary: Co-immunoprecipitation work from the Thony-Meyer laboratory placing CcmE in complexes with other Ccm components (GOA lists CcmC as the partner). The interaction is real, but generic protein binding does not convey CcmE's function.

Reason: Following the protein-binding policy, the bare GO:0005515 term is removed as uninformative; this does not dispute the reported CcmE interactions. CcmE's interactions with CcmC (heme loading) and CcmF (heme delivery) are steps in its heme-chaperone cycle, which is captured by heme binding (GO:0020037) and cytochrome c-heme linkage (GO:0018063). No more informative MF term exists for the chaperone-partner contact itself.

Summary: CcmE forms a ternary CcmCDE complex with CcmC and CcmD during heme loading. The interaction is well supported, but bare protein binding is uninformative.

Reason: Protein-binding policy: the CcmC-CcmE interaction is the heme-loading step of CcmE's chaperone cycle and is better represented by heme binding and the cytochrome c-heme linkage process. Removal does not mean the interaction is false.

Summary: CcmE variants co-precipitate with CcmC, mapping the CcmC interaction to the periplasmic heme-binding domain of CcmE. Bare protein binding is uninformative.

Reason: Protein-binding policy: the reported CcmC interaction is accepted as real but removed as a function annotation because GO:0005515 does not describe what CcmE does; its heme-chaperone role is captured elsewhere.

Summary: Holo-CcmE binds CcmC in a stable dead-end complex when CcmA or CcmB is absent, and CcmAB-dependent ATP hydrolysis releases it. Bare protein binding is uninformative.

Reason: Protein-binding policy: the CcmC-holoCcmE complex is a trafficking intermediate of the heme-chaperone cycle, not a distinct binding function of CcmE. Removal does not dispute the interaction.

Summary: Purified GST-CcmCDE complexes trapped with heme show CcmE bound to CcmC. The interaction is solid, but generic protein binding conveys no function.

Reason: Protein-binding policy: the CcmCDE complex is the site of covalent heme loading onto CcmE (His130), which is better captured by heme binding and the cytochrome c-heme linkage process. Removal does not mean the interaction is false.

Summary: CcmE is a monotopic inner (cytoplasmic) membrane protein whose N-terminal helix anchors a periplasmic heme-binding domain.

Reason: Experimental work describes CcmE as a monotopic membrane protein with a periplasmic functional domain, and its membrane anchor is functionally important for heme receipt from CcmC. Plasma membrane is the correct location term for the E. coli inner membrane.

Summary: CcmE is itself covalently linked to heme through His130 before delivering that heme to apocytochrome c.

Reason: CcmE supplies His130 to its covalent heme-protein intermediate before delivering heme downstream. The general protein-heme linkage row explicitly captures that chemical participation. GO:0018063 currently includes other heme proteins as well as cytochromes, so CcmE is not excluded by its name; its later donor role in cytochrome maturation is separately represented by the retained linkage replacements. The redundant historical NEW proposal is retired in place, with its original source payload preserved for provenance; the supported biological claim remains active through the replacements.

Summary: CcmE contributes to c-type cytochrome maturation; cytochrome complex assembly is a broad parent of the more precise process.

Reason: GO:0018063 cytochrome c-heme linkage is an is_a descendant of GO:0017004 and names the specific step CcmE serves (delivery of heme for covalent attachment to apocytochrome c). Cytochrome complex assembly otherwise suggests assembly of multi-subunit cytochrome complexes, which CcmE does not directly perform.

Proposed replacements: cytochrome c-heme linkage

Summary: The Mavridou et al. study describes CcmE as the pivotal heme chaperone in cytochrome c biogenesis; the correct but general process is refined as for the IEA row.

Reason: Consistent with the IEA row for the same term: the claim is sound but the is_a descendant cytochrome c-heme linkage (GO:0018063) is the precise process supported for CcmE.

Proposed replacements: cytochrome c-heme linkage

Summary: Heme binding is conserved across the CcmE/CycJ family, including plant mitochondrial CCME; E. coli CcmE is among the experimental donors.

Reason: The PAINT node places heme binding at the root of the CcmE family, and E. coli CcmE has direct experimental evidence (its own appearance in the WITH/FROM reflects this grounding). Heme binding is CcmE's core molecular activity as a heme chaperone.

Summary: Schulz et al. showed that CcmE binds heme in the periplasm via a single covalent bond to a histidine, defining it as a heme chaperone.

Reason: Direct biochemical demonstration of heme binding by CcmE; this is the founding evidence for its chaperone function and the core MF.

Summary: InterPro CcmE family mapping to heme binding; consistent with the experimental evidence.

Reason: Same claim as the IBA and IDA rows; the CcmE family signature is a sound basis and the activity is directly demonstrated for E. coli CcmE.

Summary: CcmABCD/E assembly is demonstrated, but its fit to an ATP-binding cassette transporter complex remains mechanistically contested.

Reason: Structures establish association with the ABC-family machinery, including bound CcmE. GO:0043190 describes a metabolite-transport complex, not just ABC architecture. The 2023 floppase interpretation and 2025 ATP-independent CcmCD/ATP-dependent release interpretation disagree about coupling and conduit. Retain uncertainty about this functional complex class rather than treating the older rejection or the newer architecture as decisive.

Summary: CcmE family members are required for c-type cytochrome biogenesis; E. coli CcmE is a descendant with experimental support.

Reason: Correct and well supported phylogenetically and experimentally. CcmE carries the heme that becomes covalently attached to cytochrome c, so it contributes directly to cytochrome c biosynthesis.

Summary: Purification of CcmCDE heme-trapped intermediates and holo-CcmE defines CcmE's position in the heme trafficking route to cytochrome c.

Reason: The paper biochemically defines holo-CcmE formation and its oxidized heme state as an intermediate en route to the CcmF/H synthetase, supporting CcmE's role in cytochrome c biosynthesis.

Summary: CcmE is essential for cytochrome c maturation, and its covalently bound heme is delivered to apocytochrome c.

Reason: Mutant and heme-transfer evidence in the founding paper establish CcmE as an essential participant in cytochrome c biosynthesis.

Summary: The asserted heme import direction is opposite to the system I maturation route.

Reason: The checked GO definition requires movement from outside the cell across the plasma membrane into the cytosol. System I handles cytoplasmically synthesized heme for periplasmic maturation. Neither competing export model supports cytosolic import. This direction mismatch, rather than a blanket rejection of heme transport, is the reason for removal.

Summary: Retired historical proposal; the same supported process is already supplied by the two MODIFY replacements for cytochrome complex assembly.

Reason: This historical NEW row adds no coverage beyond the existing GO:0017004 rows refined to GO:0018063. It is retired as a duplicate proposal, not rejected as biologically false. CcmE is a heme-transfer participant and the process remains in its core function and replacement terms. The row's position, term, original evidence/reference/qualifier and historical NEW action are retained; retired marks it as inactive rather than asserting another proposal.